Project information

What are the goals of the Microbiome Immunity Project?

The Microbiome Immunity Project aims to help scientists understand how trillions of bacteria in our bodies impact diseases such as Type 1 diabetes and Crohn's disease.

The primary goal of the project is therefore to generate a set of predicted protein structures of the entire human microbiome, containing around 3 million unique genes. This will help scientists determine the role played by these bacteria. Another goal is to share the results of the project with scientists around the world to further facilitate research on diseases implicated with the microbiome.

How are the goals of the project being met?

The Microbiome Immunity Project will meet its goals by using a computational research technique called protein structure prediction. This is a process through which computers simulate how a protein 1-dimensional sequence folds into its final 3-dimensional structure. (For more information about computational protein folding, see the Human Proteome Folding project.)

Knowing the structures of proteins of the microbiome can help researchers predict the functions of these proteins. An understanding of the role of these proteins will then help scientists develop drugs to control them or inhibit harmful interactions and therefore help treat diseases that originate in or are influenced by the human microbiome.

Who are the scientists involved in this study?

The Microbiome Immunity Project brings together researchers at the Broad Institute of MIT and Harvard, Massachusetts General Hospital, University of California San Diego and the Simons Foundation’s Flatiron Institute.

The Broad Institute brings expertise on the role of the human microbiome in health and disease to the project. By coupling microbiome analysis with the clinical knowledge at Massachusetts General Hospital, they analyze data generated from individuals with these diseases to prioritize genes from bacteria that are relevant in autoimmune diseases such as Inflammatory Bowel Disease and Type 1 Diabetes.

The Knight Lab at the University of California San Diego brings knowledge on and expertise in microbial genomes. They prepare input data for World Community Grid based on information from the Broad Institute. After obtaining results from World Community Grid, with the help of the Flatiron Institute, they annotate protein functions inferred from structures. The Knight Lab will also coordinate efforts to predict protein-protein interactions and design small molecules. They will also build a resource to collect all of the Microbiome Immunity Project predictions and share them with researchers from around the world.

The Flatiron Institute provides the expertise in predicting protein structure and function. They will work with the Knight Lab to further develop these codes to predict large microbial protein families, about which little is currently known.

How might the data generated on this project be useful to researchers?

The project's structure and function predictions for each of the proteins encoded by each unique gene in the human gut microbiome will be made available as an online resource for researchers interested in furthering the impact of this project.

Knowledge about gene function is critical for understanding not only which bacteria live in a specific environment, but what they actually do. By compiling their function predictions, the research team will greatly enhance the repertoire of annotated genes, and therefore help other researchers to better understand what specific microbes or communities of microbes are doing.

Additionally, the researchers aim to design small molecules (i.e. drug candidates) which inhibit harmful interactions between microbial and human proteins in Type 1 diabetes and inflammatory bowel disease. Designing an effective drug is an extremely complicated and laborious process, so through scientific publications the research team will encourage other researchers to investigate those molecules further and open up avenues for entirely new therapeutics.

Has this kind of research been attempted before? If so, how is this different?

It is only now that, for the first time, scientists can bring progress in next generation sequencing and their knowledge and understanding of microbes, together with massive computational power and newer algorithms to accurately predict structures and functions of hundreds of thousands (or more) of proteins!

For decades, scientists have studied both proteins and their structures, as well as microbes and how they impact human health. However, those studies were greatly limited in terms of their scale (e.g. by studying one microbe at a time) and scope. Similarly, structures of individual proteins have been experimentally determined since 1958 and computational investigations of protein structures began in early 1970s.

A turning point came in the early 2000s with the introduction of next generation sequencing, due to progress in computing power and the development of new algorithms. Thanks to next generation sequencing, obtaining DNA sequences encoding genes became much cheaper and quicker.

Around the same time new tools, such as Rosetta (which is being used for this project), were being developed to computationally predict protein structure and were, in fact, used for the Human Proteome Folding project on World Community Grid.

Since then, these tools have been refined and enhanced. Combined with the massive computational resources of World Community Grid, a project of this scale has only now become possible.

How is World Community Grid helping with this effort?

While effective, protein folding simulations are resource-intensive and often require more computational power than scientists typically have access to. The Microbiome Immunity Project research team is therefore enlisting the help of World Community Grid volunteers, each of whom runs these simulations on their computers. Each of these simulations is a virtual experiment to predict the structure of a protein.

The massive amount of aggregated computation power World Community Grid brings to this project will greatly advance and accelerate this new area of health research.

How can I help?

Anyone with a computer can help scientists understand how the human microbiome impacts disease, simply by joining World Community Grid.

It's easy: you create a World Community Grid account, select to support the Microbiome Immunity Project and then install our free and safe software on your computer. Then, whenever your computer has any unused computing power, it runs a simulation on behalf of the Microbiome Immunity Project team. The more people that participate, the quicker the researchers can get their work done!